Influenza infection causes an estimated 1 million deaths worldwide yearly. Severe influenza respiratory disease is more common in children with conditions such as prematurity-related chronic lung disease. Influenza vaccine immunogenicity is modest in children, and influenza vaccines have been incompletely studied in premature infants. The overall goals of this project are to test the hypothesis that live attenuated influenza vaccine (LAIV) will be immunologically superior, with an acceptable side-effect profile, to trivalent, inactivated influenza vaccine (TIV) in former premature infants, and to provide extensive, sophisticated explication of the humoral and cellular immune responses of premature infants to influenza immunization. The overall goal of this planning grant is to consolidate, within the context of an established, collaborative group of centers investigating premature infant vaccine responses, all necessary capacity for a clinical trial of LAIV in former premature infants. The specific aims and research plan of this planning grant are: Specific Aim 1. To sharpen the assumptions concerning immunogenicity and safety of influenza vaccines in former preterm (PT) infants. Previous data collected by the collaborative group on TIV administration to PT infants will be used to refine assumptions for vaccine immunogenicity and safety monitoring of the clinical trial. Specific Aim 2. To prepare and submit an investigational new drug (IND) application to the US Food and Drug Administration (FDA). Since the investigational vaccine (LAIV) would be used in children below the licensed age group (=2 years), administration would require IND application. Specific Aim 3. To refine methods for the clinical trial. Experience from previously conducted trials and ongoing laboratory work by the collaborative group will be used further to develop study methods, with particular attention to subject enrollment, web-based data management, influenza identification, telephone assessment, cellular immunology methods and safety and analysis methods. Specific Aim 4. To complete a clinical protocol and associated documents for the clinical trial. The collaborative group will develop a complete protocol, consent forms, manual of operations, data and safety monitoring plans, and institutional review board submission materials. The specific aims of the clinical trial for which this planning grant is requested would be: Specific Aim 1. To measure the differences in safety and humoral and cellular immunogenicities between trivalent, inactivated, split-virion influenza vaccine (TIV) and live, attenuated, trivalent, influenza vaccine (LAIV) in former very (=32 weeks'gestation at birth) preterm (PT), very-low-birth-weight (VLBW, = 1500 grams at birth) infants who are receiving their first series of influenza vaccine. Specific Aim 2. To measure the differences in safety and humoral and cellular immunogenicities between TIV and LAIV in former VLBW infants who are receiving their second series of influenza vaccine.